INTRODUCTION: Increased high-sensitivity c-reactive protein (hs-CRP) is a potent independent predictor of future first cardiac events in healthy adults. However, the determinants of hs-CRP have yet to be clearly defined, and longitudinal data are lacking. PROPOSED STUDY: We have stored sera from a longitudinal study of the seasonal variation in blood cholesterol (SEASON; NHLBI RO1 HL 52745) in which blood samples were collected at baseline, and quarterly for 1 year. This study was entirely observational, subjects were assessed at multiple time points in a free living environment. The data set contains meticulous longitudinal measures of anthropometric characteristics (body mass, BMI, waist: hip ratio), physical activity and dietary intake (12-15 24 hr physical activity and diet recalls), serum lipids and lipoproteins, blood pressure, smoking, ethnicity, socio-economic status, education, demographic factors, recent infection history, and psychological factors. We propose to measure hs-CRP in the stored sera of these subjects, and use the results together with the previously collected data to study the determinants of hs-CRP. SPECIFIC AIM: To measure hs-CRP in stored sera of healthy men and women (n=621) who participated in the SEASON study (NHLBI RO1 HL 52745) and to examine the determinants of hs-CRP. PRIMARY HYPOTHESIS: BMI will be the strongest predictor of hs-CRP. SECONDARY HYPOTHESES: Dietary glycemic load, omega 3 fatty acid intake, and depression will be secondary determinants of hs-CRP.